RESUMEN
AIMS: To investigate the role of genetic testing in patients with idiopathic atrioventricular conduction disease requiring pacemaker (PM) implantation before the age of 50 years. METHODS AND RESULTS: All consecutive PM implantations in Southern Switzerland between 2010 and 2019 were evaluated. Inclusion criteria were: (i) age at the time of PM implantation: < 50 years; (ii) atrioventricular block (AVB) of unknown aetiology. Study population was investigated by ajmaline challenge and echocardiographic assessment over time. Genetic testing was performed using next-generation sequencing panel, containing 174 genes associated to inherited cardiac diseases, and Sanger sequencing confirmation of suspected variants with clinical implication. Of 2510 patients who underwent PM implantation, 15 (0.6%) were young adults (median age: 44 years, male predominance) presenting with advanced AVB of unknown origin. The average incidence of idiopathic AVB computed over the 2010-2019 time window was 0.7 per 100 000 persons per year (95% CI 0.4-1.2). Most of patients (67%) presented with specific genetic findings (pathogenic variant) or variants of uncertain significance (VUS). A pathogenic variant of PKP2 gene was found in one patient (6.7%) with no overt structural cardiac abnormalities. A VUS of TRPM4, MYBPC3, SCN5A, KCNE1, LMNA, GJA5 genes was found in other nine cases (60%). Of these, three unrelated patients (20%) presented the same heterozygous missense variant c.2531G > A p.(Gly844Asp) in TRPM4 gene. Diagnostic re-assessment over time led to a diagnosis of Brugada syndrome and long-QT syndrome in two patients (13%). No cardiac events occurred during a median follow-up of 72 months. CONCLUSION: Idiopathic AVB in adults younger than 50 years is a very rare condition with an incidence of 0.7 per 100 000 persons/year. Systematic investigations, including genetic testing and ajmaline challenge, can lead to the achievement of a specific diagnosis in up to 20% of patients. Heterozygous missense variant c.2531G > A p.(Gly844Asp) in TRPM4 gene was found in an additional 20% of unrelated patients, suggesting possible association of the variant with the disease.
Asunto(s)
Bloqueo Atrioventricular , Marcapaso Artificial , Adulto Joven , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Trastorno del Sistema de Conducción Cardíaco/complicaciones , Bloqueo Atrioventricular/diagnóstico , Bloqueo Atrioventricular/epidemiología , Bloqueo Atrioventricular/genética , Marcapaso Artificial/efectos adversos , Pruebas Genéticas , AjmalinaRESUMEN
Aims: Subcutaneous implantable cardioverter-defibrillator (S-ICD) can avoid important complications associated with transvenous leads in patients with inherited primary arrhythmia syndromes, who do not need pacing therapy. Few data are available on the percentage of patients with inherited arrhythmia syndromes eligible for S-ICD implantation. Aim of this study was to analyse the eligibility for S-ICD in a series of patients with Brugada syndrome (BrS), and to compare it with patients with other channelopathies. Methods and results: Patients presenting with BrS, long-QT syndrome (LQTS), early repolarization syndrome (ERS), and idiopathic ventricular fibrillation (IVF) were considered eligible for this study. ECG screening was performed by analysis of QRS complex and T wave morphology recorded in standing and supine position. Eligibility was defined when ≥1 sense vector was acceptable in both supine and standing position. A total of 100 patients (72 males; mean age: 46 ± 17 years) underwent S-ICD sensing screening. Sixty-one patients presented with BrS, 21 with LQTS, 14 with IVF, and 4 with ERS. Thirty-four patients with BrS (56%) presented with spontaneous type 1 ECG. In the other 27 patients (44%), type 1 ECG was unmasked by ajmaline. Overall, rate of screening failure was 13%. Patients with BrS had a higher rate of inappropriate morphology analysis as compared with other channelopathies (18% vs. 5%, P = 0.07) and had a lower number of suitable sensing vectors (49.6% vs. 84.7% vs. P < 0.001). Ajmaline challenge unmasked sensing failure in 14.8% of drug-induced BrS patients previously considered eligible. In all patients, the reason for sensing inappropriateness was due to the presence of high T wave voltages. Conclusion: S-ICD screening failure occurs in up to 13% of patients with inherited primary arrhythmia syndromes. Patients with BrS present a higher rate of screening failure as compared with other cardiac channelopathies.
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Síndrome de Brugada/diagnóstico , Síndrome de Brugada/cirugía , Toma de Decisiones Clínicas , Desfibriladores Implantables , Cardioversión Eléctrica/instrumentación , Electrocardiografía , Determinación de la Elegibilidad , Selección de Paciente , Adulto , Síndrome de Brugada/genética , Síndrome de Brugada/fisiopatología , Europa (Continente) , Femenino , Predisposición Genética a la Enfermedad , Herencia , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Tokio , VectorcardiografíaRESUMEN
Aims: Out-of-hospital cardiac arrest (OHCA) in the absence of evident structural heart disease is rare and can be due to subclinical cardiomyopathy and primary electrical disorders, including idiopathic ventricular fibrillation (IVF) with early repolarization (ER) pattern. Aim of this study was to investigate prevalence, clinical features, and long-term prognosis of IVF in OHCA survivors with otherwise normal 12-lead electrocardiograms (ECGs). Methods and Results: Patients with IVF in the absence of ER pattern or atrioventricular conduction abnormalities were considered eligible for this study. A total of 3407 OHCAs occurred in our region from 2000 to 2014. Out-of-hospital cardiac arrests of presumed cardiac origin were 2192; of them, 644 presented with a ventricular arrhythmia (VT/VF) as first shockable rhythm. Among them, a total of 74 implantable cardioverter-defibrillators were implanted for secondary prevention. Ventricular arrhythmia was considered idiopathic in 11 (15%) of these patients. Over a mean follow-up time of 85 ± 47 months (median: 42 months), ECG was found abnormal in three cases. In the remaining eight patients (6 males; median age: 45 years), no ECG or structural abnormalities were detected during the follow-up. Prevalence of IVF in OHCA survivors with first-shockable rhythm was 1.2%. During the long-term follow-up, no patient died or experienced ICD interventions. No new echocardiographic abnormal findings were revealed. Conclusion: Idiopathic ventricular fibrillation is rare occurring in 1.2% of OHCA survivors presenting with a shockable rhythm. The initial diagnosis can change in up to 27% of cases. Patients with IVF and no ER pattern or AV conduction disturbances have a good prognosis during a long-term follow-up.
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Paro Cardíaco Extrahospitalario/epidemiología , Sobrevivientes , Fibrilación Ventricular/epidemiología , Desfibriladores Implantables , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/prevención & control , Prevalencia , Prevención Secundaria , Suiza/epidemiología , Fibrilación Ventricular/terapiaRESUMEN
AIM: To determine the incidence of out-of-hospital cardiac arrest (OHCA) fulfilling Utstein criteria in the Canton Ticino, Switzerland, the survival rate of OHCA patients and their neurological outcome. METHODS AND RESULTS: All OHCAs treated in Canton Ticino between 1 January 2005 and 31 December 2014 were followed until either death or hospital discharge. The survival and neurological outcome of those OHCA fulfilling Utstein criteria are reported. A total of 3367 OHCAs occurred in the Canton Ticino over a 10-year period. Resuscitation was attempted in 2298 patients; of those 1492 (65%) were of presumed cardiac origin, 454 fulfilling the Utstein comparator criteria. About 69% [95% confidence interval (CI), 66.6-71.4%] of the patients had a bystander-witnessed arrest; a dispatched cardiopulmonary resuscitation (CPR) steadily and significantly increased from 2005 to 2014. Out-of-hospital cardiac arrest occurred prevalently home (67%), in men (71%) of a mean age of 71 ± 13 years. There were no statistically significant differences either in demographic characteristics of OHCA victims over these years or in presenting rhythm. There was a progressive increase in the survival at discharge from 15% in 2005 to 55% in 2014; overall 96% (95% CI, 93.3-99.9%) of the survivors had a good neurological outcome. CONCLUSION: The significant increase in Utstein comparator survival rates and improved neurological outcome in OHCA victims in Canton Ticino are the result of an effective OHCA management programme which includes large-scale public education, a coordinated fast EMS response, high density of external defibrillators, and advances in clinical interventions for OHCAs.
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Servicios Médicos de Urgencia , Sistema Nervioso/fisiopatología , Paro Cardíaco Extrahospitalario/terapia , Resucitación , Anciano , Anciano de 80 o más Años , Femenino , Mortalidad Hospitalaria , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Examen Neurológico , Paro Cardíaco Extrahospitalario/diagnóstico , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/fisiopatología , Alta del Paciente , Recuperación de la Función , Sistema de Registros , Resucitación/efectos adversos , Resucitación/mortalidad , Factores de Riesgo , Análisis de Supervivencia , Suiza/epidemiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this study was to determine overall and aetiology-related incidence of secondary prevention ICD implantation over the last 15years in Canton Ticino and to assess clinical outcome according to time period of implantation. METHODS AND RESULTS: Consecutive patients treated by implantation of an ICD for secondary prevention from 2000 to 2015 were included in the current study and compared between 5-year cohorts (2000/2004; 2005/2009; 2010/2015). Yearly implantation rate, changing in clinical presentation over years and events during follow-up were evaluated. One-hundred fifty six patients were included. ICD implantation rate increased from 2.1 in 2000-2005 to 5.1 in 2010-2015, respectively (p 0.001). There was an increase in the proportion of non-ischaemic patients and of ventricular tachycardia (VT) as presenting rhythm. No differences in appropriate ICD interventions were observed according to aetiology, presenting arrhythmia or type of device. Reverse remodelling was observed more often in non-ischaemic patients, without any influence on the occurrence of appropriate interventions. Previous myocardial infarction (MI), atrial fibrillation (AF), NYHA class 2-3 and left ventricular ejection fraction (LVEF)<35% were predictors of appropriate therapies during follow-up. CONCLUSIONS: Rate of implants for secondary prevention indication has almost doubled during the last 15years. Importantly, there has been a progressive increase of non-ischaemic patients receiving an ICD, and of VT as presenting rhythm. Patients had an overall good survival and a relatively low incidence of appropriate therapies. Improvement of ejection fraction did not correlate with risk reduction of ventricular arrhythmias.
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Desfibriladores Implantables , Cardioversión Eléctrica , Implantación de Prótesis/tendencias , Prevención Secundaria , Taquicardia Ventricular , Anciano , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables/estadística & datos numéricos , Desfibriladores Implantables/tendencias , Cardioversión Eléctrica/instrumentación , Cardioversión Eléctrica/métodos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Implantación de Prótesis/métodos , Prevención Secundaria/métodos , Prevención Secundaria/tendencias , Análisis de Supervivencia , Suiza/epidemiología , Taquicardia Ventricular/epidemiología , Taquicardia Ventricular/etiología , Taquicardia Ventricular/prevención & controlRESUMEN
AIMS: The aim of the study was to retrospectively evaluate safety and patient satisfaction of same-day discharge after elective radial coronary angiography/percutaneous coronary intervention (PCI) after the implementation of a radial lounge facility. METHODS: All patients admitted to our radial lounge with a planned same-day discharge after an uncomplicated coronary angiography/PCI, having a co-living caregiver, were day enrolled in the study. Rates of same-day discharge, unplanned overnight stay, and in-hospital and first complications [death, myocardial infarction (MI), unplanned coronary angiography, access site hematoma, bleedings requiring hospitalization] were analysed; satisfaction was also evaluated through a questionnaire. RESULTS: From February 2015 to January 2016, 312 patients with a mean age of 66.6â±â10.8 years were admitted to the radial lounge (coronary angiography, nâ=â232; PCIs, nâ=â80). Of them, 245 (78.5%) were discharged the same day. Mean radial lounge monitoring was 6:35âh (interquartile range 5:30-7:30âh). No episodes of death/MI/unplanned coronary angiography were observed both in same-day discharged and postponed patients. Reasons to postpone discharge were: PCI deemed to need prolonged monitoring in 31, patient's preference in 14, femoral shift in 13, surgery in four, chest pain in four, and bleeding in one. At day 1, 11 access site hematoma and one hospitalization for access site bleeding were reported. Patients reported complete satisfaction in 97% of cases. Unplanned overnight stay was common among PCIs patients (RR 6.2, 95% CI 3.9-9.9, Pâ<â0.001). CONCLUSION: A low rate of minor complications was observed in elective radial coronary angiography and PCIs showing the feasibility and safety of the development of an institutional protocol for same-day discharge after the implementation of a radial lounge facility.
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Enfermedad de la Arteria Coronaria/cirugía , Alta del Paciente/normas , Satisfacción del Paciente/estadística & datos numéricos , Intervención Coronaria Percutánea , Anciano , Angiografía Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Estudios Retrospectivos , Suiza , Factores de TiempoRESUMEN
BACKGROUND: Ventricular fibrillation is one of the leading causes of death in North America. Brugada syndrome is characterized by ST segment elevation on the right precordial leads V1 through V3 and right bundle branch block, and may cause sudden death. Mutations in the SCN5A gene encoding the cardiac voltage-gated Na+ channel (hNav1.5) are associated with Brugada syndrome. OBJECTIVES: In this study, three novel mutations on the SCN5A gene were identified and characterized in different patients with Brugada syndrome. METHODS: Blood samples were collected from patients with Brugada syndrome for gene screening. Mutations found on the SCN5A gene in these patients were reproduced in vitro on hNav1.5 background. Wild type and mutant channels expressed in tsA201 cells were characterized using the patch clamp technique in whole cell configuration and/or confocal microscopy. RESULTS: No current could be recorded from cells expressing the hNav1.5/G1740R mutant, incubated at 37 degrees C. However, at a lower incubation temperature (22 degrees C), macroscopic Na+ currents were recorded. Confocal microscopy study confirmed that at 37 degrees C, hNav1.5/G1740R mutant channels were retained in the endoplasmic reticulum. The E473X and N1774+12X mutants produced truncated proteins and did not express any currents; however, coexpression of each of these mutants with wild type channels shows 50% reduction of Na+ currents. CONCLUSION: This study confirms that the loss of function of cardiac Na+ channels is the basis of the Brugada syndrome clinical phenotype.